A pre-specified analysis of the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) randomized controlled trial on the incidence of abrupt declines in kidney function
Hiddo J.L. Heerspink, David Z.I. Cherney, Douwe Postmus, Bergur V. Stefánsson, Glenn M. Chertow, Jamie P. Dwyer, Tom Greene, Mikhail Kosiborod, Anna Maria Langkilde, John J.V. McMurray, Ricardo Correa‐Rotter, Peter Rossing, C. David Sjöström, Robert D. Toto, David C. Wheeler, Hiddo J.L. Heerspink, David C. Wheeler, Glenn M. Chertow, Ricardo Correa‐Rotter, Tom Greene, Fan Fan Hou, John J.V. McMurray, Peter Rossing, Robert D. Toto, Bergur V. Stefánsson, Anna Maria Langkilde, Laura Maffei, Pablo Raffaele, S. Solís, César A. Arias, Dov Aizenberg, Carolina Lúquez, Cesar Javier Zaidman, Natalia Cluigt, M. Mayer, Andres Alvarisqueta, A. Wassermann, Rafaël Maldonado, J. Bittar, M. Maurich, L.E. Gaite, Néstor H. García, Louise E. Sivak, Pablo Ramallo, Juan Carlos Santos, Ruben Garcia Duran, Juan Oddino, A Marañón, Lília Nigro Maia, Dánae Duana Ávila, Elvino Barros, Maria H Vidotti, Daniel Panarotto, Irene de Lourdes Noronha, Luiz Alberto Andreotti Turatti, Luciane Mônica Deboni, María Eugênia Fernandes Canziani, Miguel C. Riella, Marcelo Rodrigues Bacci, Raphael Paschoalin, R. J. Franco, João Carlos Goldani, Eric St-Amour, Andrew Steele, R. Goldenberg, Sanjay Pandeya, Harpreet S. Bajaj, David Z.I. Cherney, Stéphanie Kaiser, James Conway, Sharron Chow, G. HOWARD BAILEY, Jean‐Philippe Lafrance, Jonathan Winterstein, S. Cournoyer, D. Gaudet, F. Madore, Robyn L. Houlden, Aaron Dowell, Michel R. Langlois, Nicola Muirhead, Hasnain Khandwala, Adeera Levin, Fan Fan Hou, Ying Xue, Lingyan Zuo, Chuan‐Ming Hao, Zhaohui Ni, C. Xing, N. Chen, Yugang Dong, Rong Zhou, Xiao Xu, Yiping Zou, Chu Wang, Liu B, Qian Chen, Miao Lin, Qing Luo, D. Zhang
Abstract
This pre-specified analysis of DAPA-CKD assessed the impact of sodium-glucose cotransporter 2 inhibition on abrupt declines in kidney function in high-risk patients based on having chronic kidney disease (CKD) and substantial albuminuria. DAPA-CKD was a randomized, double-blind, placebo-controlled trial that had a median follow-up of 2.4 years. Adults with CKD (urinary albumin-tocreatinine ratio 200-5000 mg/g and estimated glomerular filtration rate 25-75 mL/min/1.73m 2 ) were randomized to dapagliflozin 10 mg/day matched to placebo (2152 individuals each). An abrupt decline in kidney function was defined as a pre-specified endpoint of doubling of serum creatinine between two subsequent study visits. We also assessed a post-hoc analysis of investigator-reported acute kidney injury-related serious adverse events. Doubling of serum creatinine between two subsequent visits (median time-interval 100 days) occurred in 63 (2.9%) and 91 (4.2%) participants in the dapagliflozin and placebo groups, respectively (hazard ratio 0.68 [95% confidence interval 0.49, 0.94]). Accounting for the competing risk of mortality did not alter our findings. There was no heterogeneity in the effect of dapagliflozin on abrupt declines in kidney function based on baseline subgroups. Acute kidney injury-related serious adverse events were not significantly different and occurred in 52 (2.5%) and 69 (3.2%) participants in the dapagliflozin and placebo groups, respectively (0.77 [0.54, 1.10]). Thus, in patients with CKD and substantial albuminuria, dapagliflozin reduced the risk of abrupt declines in kidney function.